Malaria Vaccine Can Cause Negative 'Rebound Effect,' Study Says

A new study looked at the long-term effects of the vaccine.

n this Oct. 30, 2009 file photo, a mother holds her baby as she receives a new malaria vaccine as part of a trial. Image: Karel Prinsloo/AP

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A vaccine for malaria has been a long-time dream for researchers, but it's no easy feat. Now, a new study on our most advanced vaccine shows its efficacy not only wanes, but it can also make some kids get more bouts of malaria later in life.

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In a seven-year follow up of the Phase II trial of the RTS,S vaccine—the malaria vaccine that has been in development the longest—researchers found the vaccine significantly dropped in efficacy over time.

In fact, for some areas with high rates of malaria, the vaccine actually had a negative effect, according to the paper published in the New England Journal of Medicine Wednesday.

"We don't know the extent of the problem. I think it raises a question that needs to be followed up on," Dr. Philip Bejon, Director of the Wellcome-KEMRI-Oxford Collaborative Research Programme and co-author of the study, told me on the phone from Kenya.

Early in the trial, the vaccine was fairly effective, with a 27 percent efficacy against a first episode of malaria after vaccination. But over time, the efficacy waned: By the end of seven years, the overall efficacy was 4.4 percent.

What's more worrisome is that, in areas where trial participants had high exposure to malaria, there was a negative effect: Those vaccinated actually got more cases of malaria than the control group by the end of the trial.

The researchers dubbed this effect "malaria rebound." This is because the vaccine protects against sporozoites—kind of the "baby" malaria parasites that enter the blood stream when an infectious mosquito bites a human—but it doesn't produce immunity to the later stage parasites. When children with high exposure to malaria are vaccinated, they're protected at first, but are not able to build up a natural immunity that comes from infection, and end up getting sick more often later, the authors suggest.

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But Bejon pointed out that the results are far from conclusive. For one, the sample size was quite small, with only 312 children completing the full seven-year follow up.

"With the study size that we've got, I think all we can say is that there isn't a clear benefit overall by the time you get to the end of seven years," Bejon explained. "Because of the sample size, the confidence intervals for both the negative effect in the subgroup and the positive effect overall overlap zero. So the effect size we're seeing is relatively marginal."

The Phase II trial also only doled out three doses of the vaccine, but the Phase III trial used four doses with better success. Right now, researchers are following up on the Phase III trial to see the long term effects, the results of which will come out some time next year. In the meantime, the World Health Organization has approved a much larger pilot study of the vaccine that's currently in the planning stages.

For a long time, a malaria vaccine has been the holy grail pursuit of public health research, and there are dozens of other candidates in the pipeline. Bejon said that this paper contributes to our understanding of this first generation vaccine, but that a vaccine was never going to be a magic bullet for malaria.

"You can get some quantifiable protection in the field with one antigen, so it's really important to invest in this field to get better vaccines," Bejon said. "But a malaria vaccine is only going to be useful in a setting where there's already a malaria control program functioning. A vaccine would be an add on."